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Figure 4 | Cilia

Figure 4

From: Pancreatic cyst development: insights from von Hippel-Lindau disease

Figure 4

Overview of direct and indirect pVHL-regulated cell processes in an epithelial cell. The cilium (1) consists a microtubule-based axoneme (2), and a mother (3) and a daughter centriole (4). In the cell, pVHL is located in the cilium (1), the cytoplasm (5), the endoplasmic reticulum (6) and microtubules (7). The endoplasmic reticulum is the cellular compartment where trihelical collagen IV (8) is produced. pVHL binds collagen IVα2 in the endoplasmic reticulum. When pVHL-collagen IVα2 binding is perturbed, defects in the collagen network results. Integrins (9) facilitate cell-ECM (10) adhesion. Upon loss of pVHL function, misregulation of β1-integrin disturbs the fibronectin matrix assembly. The epithelial cell polarity complex PAR3-PAR6-aPKC is located at the apical membrane (11) and LGL2 at the basolateral membrane (12). Moreover, pVHL and PAR3-PAR6-aPKC are necessary for the formation of adherens junctions (13) and tight junctions (14). PAR3-PAR6-aPKC and pVHL play a role in regulation of the cilium, each capable of binding kinesin-2 (15). Functional loss of pVHL destabilizes cell polarity, partially attributable to abnormal adherens junctions [with consequent effects on the actin belt (16)] and unstable tight junctions. The relevant literature supports a scenario whereby microtubule instability as a result of pVHL dysfunction might affect PAR3-PAR6-aPKC localization, subsequently destabilizing cell polarity and cilia maintenance.

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